Substantial Improvement in Self-Reported Mental Health Following Total Hip Arthroplasty Occurs Independent of Anesthetic Technique.

BACKGROUND: The influence of anesthetic type on mental health after total hip arthroplasty (THA) is poorly understood. Adverse effects of general anesthesia (GA) on cognition following major non-cardiac surgery are well known, but mental health following THA is less well-studied. We hypothesized that neuraxial anesthesia (NA) would provide favorable mental health profiles compared with GA after THA. METHODS: Prospectively collected Patient-Reported Outcomes Measurement Information System-10 (PROMIS) Global Mental Health (GMH) scores at preoperative baseline, and 1, 3, and 6 months after THA were accessed on 4,353 patients in the Pulmonary Embolism Prevention After HiP and KneE Replacement (PEPPER) Trial (ClinicalTrials.gov: NCT02810704). Anesthesia was categorized as: general (GA), neuraxial (NA), and neuraxial with peripheral block (NAP). The GMH was assessed longitudinally and compared between groups. RESULTS: Postoperative GMH improved (P < .05) over preoperative in every anesthetic group. Groups receiving NA had higher baseline GMH scores. Improvement in GMH was diminished after GA alone and plateaued after 1 month. Adding NA or peripheral nerve block to GA conferred additional benefit to GMH improvement. CONCLUSIONS: Patient-perceived mental health improves significantly after THA regardless of anesthetic type. Patients who have higher baseline GMH scores more commonly received NA, likely due to nonsurgical care determinants; these differences in mental wellness persisted at follow-up. Adjunctive NA or peripheral nerve block favored GMH improvement, whereas solitary GA diminished GMH improvement, which plateaued after 1 month. Substantial mental health benefits of THA may overshadow subtle differences in GMH attributable to anesthetic type.

Adherence to Antimicrobial Prophylaxis Guidelines for Elective Surgeries Across 825 US Hospitals, 2019-2020.

BACKGROUND: There are limited US data assessing adherence to surgical antimicrobial prophylaxis guidelines, particularly across a large, nationwide sample. Moreover, commonly prescribed inappropriate antimicrobial prophylaxis regimens remain unknown, hindering improvement initiatives. METHODS: We conducted a retrospective cohort study of adults who underwent elective craniotomy, hip replacement, knee replacement, spinal procedure, or hernia repair in 2019-2020 at hospitals in the PINC AI (Premier) Healthcare Database. We evaluated adherence of prophylaxis regimens, with respect to antimicrobial agents endorsed in the American Society of Health-System Pharmacist guidelines, accounting for patient antibiotic allergy and methicillin-resistant Staphylococcus aureus colonization status. We used multivariable logistic regression with random effects by hospital to evaluate associations between patient, procedural, and hospital characteristics and guideline adherence. RESULTS: Across 825 hospitals and 521 091 inpatient elective surgeries, 308 760 (59%) were adherent to prophylaxis guidelines. In adjusted analysis, adherence varied significantly by US Census division (adjusted OR [aOR] range: .61-1.61) and was significantly lower in 2020 compared with 2019 (aOR: .92; 95% CI: .91-.94; P < .001). The most common reason for nonadherence was unnecessary vancomycin use. In a post hoc analysis, controlling for patient age, comorbidities, other nephrotoxic agent use, and patient and procedure characteristics, patients receiving cefazolin plus vancomycin had 19% higher odds of acute kidney injury (AKI) compared with patients receiving cefazolin alone (aOR: 1.19; 95% CI: 1.11-1.27; P < .001). CONCLUSIONS: Adherence to antimicrobial prophylaxis guidelines remains suboptimal, largely driven by unnecessary vancomycin use, which may increase the risk of AKI. Adherence decreased in the first year of the COVID-19 pandemic.

Patterns, Predictors, and Intercenter Variability in Empiric Gram-Negative Antibiotic Use Across 928 United States Hospitals.

BACKGROUND: Empiric antibiotic use among hospitalized adults in the United States (US) is largely undescribed. Identifying factors associated with broad-spectrum empiric therapy may inform antibiotic stewardship interventions and facilitate benchmarking. METHODS: We performed a retrospective cohort study of adults discharged in 2019 from 928 hospitals in the Premier Healthcare Database. "Empiric" gram-negative antibiotics were defined by administration before day 3 of hospitalization. Multivariable logistic regression models with random effects by hospital were used to evaluate associations between patient and hospital characteristics and empiric receipt of broad-spectrum, compared to narrow-spectrum, gram-negative antibiotics. RESULTS: Of 8 017 740 hospitalized adults, 2 928 657 (37%) received empiric gram-negative antibiotics. Among 1 781 306 who received broad-spectrum therapy, 30% did not have a common infectious syndrome present on admission (pneumonia, urinary tract infection, sepsis, or bacteremia), surgery, or an intensive care unit stay in the empiric window. Holding other factors constant, males were 22% more likely (adjusted odds ratio [aOR], 1.22 [95% confidence interval, 1.22-1.23]), and all non-White racial groups 6%-13% less likely (aOR range, 0.87-0.94), to receive broad-spectrum therapy. There were significant prescribing differences by region, with the highest adjusted odds of broad-spectrum therapy in the US West South Central division. Even after model adjustment, there remained substantial interhospital variability: Among patients receiving empiric therapy, the probability of receiving broad-spectrum antibiotics varied as much as 34+ percentage points due solely to the admitting hospital (95% interval of probabilities: 43%-77%). CONCLUSIONS: Empiric gram-negative antibiotic use is highly variable across US regions, and there is high, unexplained interhospital variability. Sex and racial disparities in the receipt of broad-spectrum therapy warrant further investigation.

Secretory-IgA binding to intestinal microbiota attenuates inflammatory reactions as the intestinal barrier of preterm infants matures.

Previous work has shown that Secretory-IgA (SIgA) binding to the intestinal microbiota is variable and may regulate host inflammatory bowel responses. Nevertheless, the impact of the SIgA functional binding to the microbiota remains largely unknown in preterm infants whose immature epithelial barriers make them particularly susceptible to inflammation. Here, we investigated SIgA binding to intestinal microbiota isolated from stools of preterm infants <33 weeks gestation with various levels of intestinal permeability. We found that SIgA binding to intestinal microbiota attenuates inflammatory reactions in preterm infants. We also observed a significant correlation between SIgA affinity to the microbiota and the infant's intestinal barrier maturation. Still, SIgA affinity was not associated with developing host defenses, such as the production of mucus and inflammatory calprotectin protein, but it depended on the microbiota shifts as the intestinal barrier matures. In conclusion, we reported an association between the SIgA functional binding to the microbiota and the maturity of the preterm infant's intestinal barrier, indicating that the pattern of SIgA coating is altered as the intestinal barrier matures.

Childhood adiposity, serum metabolites and breast density in young women.

BACKGROUND: Childhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its protective effect for breast cancer later in life. The objective of this study was to identify metabolites in childhood serum that may mediate the inverse association between childhood adiposity and young adult breast density. METHODS: Longitudinal data from 182 female participants in the Dietary Intervention Study in Children (DISC) and the DISC 2006 (DISC06) Follow-Up Study were analyzed. Childhood adiposity was assessed by anthropometry at the DISC visit with serum available that occurred closest to menarche and expressed as a body mass index (BMI) z-score. Serum metabolites were measured by untargeted metabolomics using ultra-high-performance liquid chromatography-tandem mass spectrometry. %DBV and ADBV were measured by magnetic resonance imaging at the DISC06 visit when participants were 25-29 years old. Robust mixed effects linear regression was used to identify serum metabolites associated with childhood BMI z-scores and breast density, and the R package mediation was used to quantify mediation. RESULTS: Of the 115 metabolites associated with BMI z-scores (FDR < 0.20), 4 were significantly associated with %DBV and 6 with ADBV before, though not after, adjustment for multiple comparisons. Mediation analysis identified 2 unnamed metabolites, X-16576 and X-24588, as potential mediators of the inverse association between childhood adiposity and dense breast volume. X-16576 mediated 14% (95% confidence interval (CI) = 0.002, 0.46; P = 0.04) of the association of childhood adiposity with %DBV and 11% (95% CI = 0.01, 0.26; P = 0.02) of its association with ADBV. X-24588 also mediated 7% (95% CI = 0.001, 0.18; P = 0.05) of the association of childhood adiposity with ADBV. None of the other metabolites examined contributed to mediation of the childhood adiposity-%DBV association, though there was some support for contributions of lysine, valine and 7-methylguanine to mediation of the inverse association of childhood adiposity with ADBV. CONCLUSIONS: Additional large longitudinal studies are needed to identify metabolites and other biomarkers that mediate the inverse association of childhood adiposity with breast density and possibly breast cancer risk.

Life-years lost due to cancer among solid organ transplant recipients in the United States, 1987 to 2014.

BACKGROUND: Solid organ transplant recipients have an elevated risk of cancer. Quantifying the life-years lost (LYL) due to cancer provides a complementary view of the burden of cancer distinct from other metrics and may identify subgroups of transplant recipients who are most affected. METHODS: Linked transplant and cancer registry data were used to identify incident cancers and deaths among solid organ transplant recipients in the United States (1987-2014). Data on LYL due to cancer within 10 years posttransplant were derived using mean survival estimates from Cox models. RESULTS: Among 221,962 transplant recipients, 13,074 (5.9%) developed cancer within 10 years of transplantation. During this period, the mean LYL due to cancer were 0.16 years per transplant recipient and 2.7 years per cancer case. Cancer was responsible for a loss of 1.9% of the total life-years expected in the absence of cancer in this population. Lung recipients had the highest proportion of total LYL due to cancer (0.45%) followed by heart recipients (0.29%). LYL due to cancer increased with age, from 0.5% among those aged birth to 34 years at transplant to 3.2% among those aged 50 years and older. Among recipients overall, lung cancer was the largest contributor, accounting for 24% of all LYL due to cancer, and non-Hodgkin lymphoma had the next highest contribution (15%). CONCLUSIONS: Transplant recipients have a shortened lifespan after developing cancer. Lung cancer and non-Hodgkin lymphoma contribute strongly to LYL due to cancer within the first 10 years after transplant, highlighting opportunities to reduce cancer mortality through prevention and screening.

Renal versus cerebral saturation trajectories: the perinatal transition in preterm neonates.

BACKGROUND: The aim of this study was to develop reference renal saturation (rSrO2) curves in premature infants, depict how they differ from cerebral saturation (rScO2) curves, and evaluate the effect of blood pressure on these values using near-infrared spectroscopy (NIRS). METHODS: This is a prospective cohort study of 57 inborn infants <12 h and <30 weeks gestation. rScO2, rSrO2, fractional tissue oxygen extraction (FTOE), and mean arterial blood pressure (MAP) were continuously monitored every 30 s for 96 h. Quantile regression was used to establish nomograms, and mean saturation values were evaluated for different MAP ranges. RESULTS: Median rSrO2 at the start of monitoring was ~10% higher than rScO2. rSrO2 showed a significant decline over time while rScO2 peaked at 26 h. FTOE demonstrated a similar but inverse trend to their saturation counterparts. rScO2 declined as MAP increased, while rSrO2 showed a peak and decline as MAP increased. CONCLUSIONS: We provide rSrO2 reference curves for the first 4 days of life, which differ in their trajectory from rScO2 and from what has previously been reported for rSrO2 in the full-term population. In addition, we observed a peak and decline in renal saturation with increasing MAP, suggesting a renovascular response to blood pressure changes. IMPACT: This article depicts reference renal saturation curves during the perinatal transition in preterm infants. We show how renal saturation compares to cerebral saturation trends over time. We describe a peak and decline in renal saturation with increasing MAP, suggesting a renovascular response to blood pressure changes.

Randomized trial of azithromycin to eradicate Ureaplasma respiratory colonization in preterm infants: 2-year outcomes.

BACKGROUND: To assess the potential impact of azithromycin treatment in the first week following birth on 2-year outcomes in preterm infants with and without Ureaplasma respiratory colonization who participated in a double-blind, placebo-controlled randomized controlled trial. METHODS: Respiratory morbidity was assessed at NICU discharge and at 6, 12, and 22-26 months corrected age using pulmonary questionnaires. Comprehensive neurodevelopmental assessments were completed between 22 and 26 months corrected age. The primary and secondary composite outcomes were death or severe respiratory morbidity and death or moderate-severe neurodevelopmental impairment, respectively, at 22-26 months corrected age. RESULTS: One hundred and twenty-one randomized participants (azithromycin, N = 60; placebo, N = 61) were included in the intent-to-treat analysis. There were no significant differences in death or serious respiratory morbidity (34.8 vs 30.4%, p = 0.67) or death or moderate-severe neurodevelopmental impairment (47 vs 33%, p = 0.11) between the azithromycin and placebo groups. Among all trial participants, tracheal aspirate Ureaplasma-positive infants experienced a higher frequency of death or serious respiratory morbidity at 22-26 months corrected age (58%) than tracheal aspirate Ureaplasma-negative infants (34%) or non-intubated infants (21%) (p = 0.028). CONCLUSIONS: We did not observe strong evidence of a difference in long-term pulmonary and neurodevelopment outcomes in preterm infants treated with azithromycin in the first week of life compared to placebo. IMPACT: No strong evidence of a difference in long-term pulmonary and neurodevelopment outcomes was identified at 22-26 months corrected age in infants treated with azithromycin in the first week of life compared to placebo. The RCT is the first study of 2-year pulmonary and neurodevelopmental outcomes of azithromycin treatment in ELGANs. Provides evidence that ELGANs with lower respiratory tract Ureaplasma have the most frequent serious respiratory morbidity in the first 2 years of life, suggesting that a Phase III trial of azithromycin to prevent BPD targeting this population is warranted.

Impact of Sex and Metabolic Comorbidities on Coronavirus Disease 2019 (COVID-19) Mortality Risk Across Age Groups: 66 646 Inpatients Across 613 U.S. Hospitals.

BACKGROUND: The relationship between common patient characteristics, such as sex and metabolic comorbidities, and mortality from coronavirus disease 2019 (COVID-19) remains incompletely understood. Emerging evidence suggests that metabolic risk factors may also vary by age. This study aimed to determine the association between common patient characteristics and mortality across age-groups among COVID-19 inpatients. METHODS: We performed a retrospective cohort study of patients discharged from hospitals in the Premier Healthcare Database between April-June 2020. Inpatients were identified using COVID-19 ICD-10-CM diagnosis codes. A priori-defined exposures were sex and present-on-admission hypertension, diabetes, obesity, and interactions between age and these comorbidities. Controlling for additional confounders, we evaluated relationships between these variables and in-hospital mortality in a log-binomial model. RESULTS: Among 66 646 (6.5%) admissions with a COVID-19 diagnosis, across 613 U.S. hospitals, 12 388 (18.6%) died in-hospital. In multivariable analysis, male sex was independently associated with 30% higher mortality risk (aRR, 1.30, 95% CI: 1.26-1.34). Diabetes without chronic complications was not a risk factor at any age (aRR 1.01, 95% CI: 0.96-1.06), and hypertension without chronic complications was a risk factor only in 20-39 year-olds (aRR, 1.68, 95% CI: 1.17-2.40). Diabetes with chronic complications, hypertension with chronic complications, and obesity were risk factors in most age-groups, with highest relative risks among 20-39 year-olds (respective aRRs 1.79, 2.33, 1.92; P-values ≤ .002). CONCLUSIONS: Hospitalized men with COVID-19 are at increased risk of death across all ages. Hypertension, diabetes with chronic complications, and obesity demonstrated age-dependent effects, with the highest relative risks among adults aged 20-39.

Significant Regional Differences in Antibiotic Use Across 576 US Hospitals and 11 701 326 Adult Admissions, 2016-2017.

BACKGROUND: Quantifying the amount and diversity of antibiotic use in United States hospitals assists antibiotic stewardship efforts but is hampered by limited national surveillance. Our study aimed to address this knowledge gap by examining adult antibiotic use across 576 hospitals and nearly 12 million encounters in 2016-2017. METHODS: We conducted a retrospective study of patients aged ≥ 18 years discharged from hospitals in the Premier Healthcare Database between 1 January 2016 and 31 December 2017. Using daily antibiotic charge data, we mapped antibiotics to mutually exclusive classes and to spectrum of activity categories. We evaluated relationships between facility and case-mix characteristics and antibiotic use in negative binomial regression models. RESULTS: The study included 11 701 326 admissions, totaling 64 064 632 patient-days, across 576 hospitals. Overall, patients received antibiotics in 65% of hospitalizations, at a crude rate of 870 days of therapy (DOT) per 1000 patient-days. By class, use was highest among ß-lactam/ß-lactamase inhibitor combinations, third- and fourth-generation cephalosporins, and glycopeptides. Teaching hospitals averaged lower rates of total antibiotic use than nonteaching hospitals (834 vs 957 DOT per 1000 patient-days; P < .001). In adjusted models, teaching hospitals remained associated with lower use of third- and fourth-generation cephalosporins and antipseudomonal agents (adjusted incidence rate ratio [95% confidence interval], 0.92 [.86-.97] and 0.91 [.85-.98], respectively). Significant regional differences in total and class-specific antibiotic use also persisted in adjusted models. CONCLUSIONS: Adult inpatient antibiotic use remains high, driven predominantly by broad-spectrum agents. Better understanding reasons for interhospital usage differences, including by region and teaching status, may inform efforts to reduce inappropriate antibiotic prescribing.

Electronically Available Patient Claims Data Improve Models for Comparing Antibiotic Use Across Hospitals: Results From 576 US Facilities.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) uses standardized antimicrobial administration ratios (SAARs)-that is, observed-to-predicted ratios-to compare antibiotic use across facilities. CDC models adjust for facility characteristics when predicting antibiotic use but do not include patient diagnoses and comorbidities that may also affect utilization. This study aimed to identify comorbidities causally related to appropriate antibiotic use and to compare models that include these comorbidities and other patient-level claims variables to a facility model for risk-adjusting inpatient antibiotic utilization. METHODS: The study included adults discharged from Premier Database hospitals in 2016-2017. For each admission, we extracted facility, claims, and antibiotic data. We evaluated 7 models to predict an admission's antibiotic days of therapy (DOTs): a CDC facility model, models that added patient clinical constructs in varying layers of complexity, and an external validation of a published patient-variable model. We calculated hospital-specific SAARs to quantify effects on hospital rankings. Separately, we used Delphi Consensus methodology to identify Elixhauser comorbidities associated with appropriate antibiotic use. RESULTS: The study included 11 701 326 admissions across 576 hospitals. Compared to a CDC-facility model, a model that added Delphi-selected comorbidities and a bacterial infection indicator was more accurate for all antibiotic outcomes. For total antibiotic use, it was 24% more accurate (respective mean absolute errors: 3.11 vs 2.35 DOTs), resulting in 31-33% more hospitals moving into bottom or top usage quartiles postadjustment. CONCLUSIONS: Adding electronically available patient claims data to facility models consistently improved antibiotic utilization predictions and yielded substantial movement in hospitals' utilization rankings.

Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus.

OBJECTIVE: We evaluated which aPL combinations increase the risk of future thrombosis in patients with SLE. METHODS: This prospective cohort study consisted of SLE patients who had been tested for all seven aPL (LA, aCL isotypes IgM, IgG and IgA, and anti-ß2-glycoprotein I isotypes IgM, IgG and IgA). Pooled logistic regression was used to assess the relationship between aPL and thrombosis. RESULTS: There were 821 SLE patients with a total of 75 048 person-months of follow-up. During the follow-up we observed 88 incident cases of thrombosis: 48 patients with arterial, 37 with venous and 3 with both arterial and venous thrombosis. In individual models, LA was the most predictive of any [age-adjusted rate ratio 3.56 (95% CI 2.01, 6.30), P < 0.0001], venous [4.89 (2.25, 10.64), P < 0.0001] and arterial [3.14 (1.41, 6.97), P = 0.005] thrombosis. Anti-ß2-glycoprotein I IgA positivity was a significant risk factor for any [2.00 (1.22, 3.3), P = 0.0065] and venous [2.8 (1.42, 5.51), P = 0.0029] thrombosis. Only anti-ß2-glycoprotein I IgA appeared to add significant risk to any [1.73 (1.04, 2.88), P = 0.0362] and venous [2.27 (1.13, 4.59), P = 0.0218] thrombosis among those with LA. We created an interaction model with four categories based on combinations of LA and other aPL to look at the relationships between combinations and the risk of thrombosis. In this model LA remained the best predictor of thrombosis. CONCLUSION: Our study demonstrated that in SLE, LA remained the best predictor of thrombosis and adding additional aPL did not add to the risk, with the exception of anti-ß2-glycoprotein I IgA.

Predictors of the start of declining eGFR in patients with systemic lupus erythematosus.

OBJECTIVE: To characterize the longitudinal trajectory of estimated glomerular filtration rate (eGFR) in patients with systemic lupus erythematosus (SLE) and identify predictors of the change in eGFR trajectory. METHODS: The longitudinal eGFR levels of patients in the Hopkins Lupus Cohort were modelled by piecewise linear regression to evaluate the slope of different line segments. The slopes were classified into declining (≤-4 mL/min/1.73 m2 per year), stable (-4 to 4 mL/min/1.73 m2 per year), and increasing (≥4 mL/min/1.73 m2 per year) states. The transition rate between states and the impact of clinical parameters were estimated by a Markov model. RESULTS: The analysis was based on 494 SLE patients. At a mean follow-up of 8.8 years, 347 (70.2%), 107 (21.7%), 33 (6.7%), and 7 (1.4%) patients had zero, one, two, and three state transitions, respectively. In patients with no transition, 37 (10.7%), 308 (88.8%), and 2 (0.6%) were in declining, stable, and increasing state, respectively. In patients with one transition, 43 (40.2%) changed from declining to stable state while 29 (27.1%) changed from stable to declining state. When patients were in a non-declining GFR state, those who were younger and African Americans were more likely to transition to a declining GFR state. In adjusted analyses, high blood pressure, C4 and low hematocrit were associated with change from non-declining to declining state. High urine protein-to-creatinine ratio also tended to be associated with change from non-declining to declining state. African American patients were less likely to move from declining to non-declining state. Use of prednisone was associated with change from declining to non-declining state. CONCLUSIONS: Patients with high blood pressure, low complement C4, low haematocrit, and high urine protein-to-creatinine ratio are more likely to have a declining eGFR trajectory, while the use of prednisone stabilizes the declining eGFR trajectory.

Anti-beta 2 glycoprotein I IgA in the SLICC classification criteria dataset.

OBJECTIVE: Anti-beta 2 glycoprotein I IgA is a common isotype of anti-beta 2 glycoprotein I in SLE. Anti-beta 2 glycoprotein I was not included in the American College of Rheumatology (ACR) SLE classification criteria, but was included in the Systemic Lupus International Collaborating Clinics (SLICC) criteria. We aimed to evaluate the prevalence of anti-beta 2-glycoprotein I IgA in SLE versus other rheumatic diseases. In addition, we examined the association between anti-beta 2 glycoprotein I IgA and disease manifestations in SLE. METHODS: The dataset consisted of 1384 patients, 657 with a consensus physician diagnosis of SLE and 727 controls with other rheumatic diseases. Anti-beta 2 glycoprotein I isotypes were measured by ELISA. Patients with a consensus diagnosis of SLE were compared to controls with respect to presence of anti-beta 2 glycoprotein I. Among patients with SLE, we assessed the association between anti-beta 2 glycoprotein I IgA and clinical manifestations. RESULTS: The prevalence of anti-beta 2 glycoprotein I IgA was 14% in SLE patients and 7% in rheumatic disease controls (odds ratio, OR 2.3, 95% CI: 1.6, 3.3). It was more common in SLE patients who were younger patients and of African descent (p = 0.019). Eleven percent of SLE patients had anti-beta 2 glycoprotein I IgA alone (no anti-beta 2 glycoprotein I IgG or IgM). There was a significant association between anti-beta 2 glycoprotein I IgA and anti-dsDNA (p = 0.001) and the other antiphospholipid antibodies (p = 0.0004). There was no significant correlation of anti-beta 2 glycoprotein I IgA with any of the other ACR or SLICC clinical criteria for SLE. Those with anti-beta 2 glycoprotein I IgA tended to have a history of thrombosis (12% vs 6%, p = 0.071), but the difference was not statistically significant. CONCLUSION: We found the anti-beta 2 glycoprotein I IgA isotype to be more common in patients with SLE and in particular, with African descent. It could occur alone without other isotypes.

Metabolic Changes in Chronic Hepatitis C Patients Who Carry IFNL4-ΔG and Achieve Sustained Virologic Response With Direct-Acting Antiviral Therapy.

BACKGROUND: Clearance of hepatitis C virus (HCV) results in rapid changes in metabolic parameters early in direct-acting antiviral (DAA) therapy. Long-term changes after sustained virologic response (SVR) remain unknown. METHODS: We investigated longitudinal changes in metabolic and inflammatory outcomes in chronic hepatitis C (CHC) patients: low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) using a general linear model for repeated measurements at 5 clinical time points and by human immunodeficiency virus (HIV) coinfection and IFNL4 genotype. RESULTS: The mean LDL increased markedly during DAA therapy (pre-DAA, 86.6 to DAA, 107.4 mg/dL; P < .0001), but then it decreased to 97.7 mg/dL by post-SVR year 1 (P < .001 compared with DAA; P = .0013 compared with SVR). In patients who carry the IFNL4-ΔG allele, mean LDL increased during treatment, then decreased at post-SVR year 1; however, in patients with TT/TT, genotype did not change during and after DAA treatment. The mean ALT and AST normalized rapidly between pre-DAA and DAA, whereas only mean ALT continued to decrease until post-SVR. Metabolic and inflammatory outcomes were similar by HIV-coinfection status. CONCLUSIONS: Changes in LDL among CHC patients who achieved SVR differed by IFNL4 genotype, which implicates the interferon-λ4 protein in metabolic changes observed in HCV-infected patients.

Continuity of Care and Mental Health Service Use Among Medicaid-enrolled Youths.

BACKGROUND: Recent reports of increased national estimates of pediatric psychiatric emergency department (ED) visits and psychiatric hospitalizations emphasize the need to research these utilization patterns. OBJECTIVES: To assess the patient-provider continuity of care (CoC) and compare the risk of psychiatric ED visits or hospitalization according to the CoC level. RESEARCH DESIGN: A cohort design was applied to Medicaid administrative claims data (2007-2014) for 3-16-year olds with a first psychiatric diagnosis between 2009 and 2013 (n=38,825). SUBJECTS: Continuously enrolled youths with (1) ≥1 outpatient psychiatric visits and (2) ≥4 pediatric outpatient visits in the prior 24 months. MEASURES: The authors assessed CoC in the 24 months before the first psychiatric outpatient visit and quantified CoC using the Alpha Index. The authors assessed patient-provider CoC before first psychiatric diagnosis and the odds of psychiatric ED visits or psychiatric hospitalizations in the year after diagnosis. RESULTS: Of the 38,825 youths, 88.9% received a first psychiatric diagnosis by age 14. The odds of ED visits were significantly higher among youths with low CoC [6.63%, adjusted odds ratio (AOR), 1.27; 95% confidence interval (CI), 1.13-1.41] or moderate CoC (5.76%; AOR, 1.14; 95% CI, 1.02-1.27) compared with those with high CoC (4.96%). Greater odds of psychiatric hospitalization related to low (7.53%; AOR, 1.17; 95% CI, 1.06-1.29) or moderate CoC (7.01%; AOR, 1.15; 95% CI, 1.03-1.27) compared with high CoC (6.06%). CONCLUSIONS: The odds of potentially disruptive clinical management and costly psychiatric ED visits or hospitalizations were lower for youths with high CoC. The findings support the need to research the impact of CoC on long-term pediatric mental health service use.

Diversity of Salmonella Typhi-responsive CD4 and CD8 T cells before and after Ty21a typhoid vaccination in children and adults.

Typhoid fever is a life-threatening disease caused by the human-restricted pathogen Salmonella enterica serovar Typhi (S. Typhi). The oral live attenuated Ty21a typhoid vaccine protects against this severe disease by eliciting robust, multifunctional cell-mediated immunity (CMI), shown to be associated with protection in wild-type S. Typhi challenge studies. Ty21a induces S. Typhi-responsive CD8+ and CD4+ T cells but little is known about the response to this vaccine in children. To address this important gap in knowledge, we have used mass cytometry to analyze pediatric and adult pre- and post-Ty21a vaccination CMI in an autologous S. Typhi antigen presentation model. Here, using conventional supervised analytical tools, we show adult T cells are more multifunctional at baseline than those obtained from children. Moreover, pediatric and adult T cells respond similarly to Ty21a vaccination, but adult responders remain more multifunctional. The use of the unsupervised dimensionality reduction tool tSNE (t-distributed Stochastic Neighbor Embedding) allowed us to confirm these findings, as well as to identify increases and decreases in well-defined specific CD4+ and CD8+ T-cell populations that were not possible to uncover using the conventional gating strategies. These findings evidenced age-associated maturation of multifunctional S. Typhi-responsive T-cell populations, including those which we have previously shown to be associated with protection from, and/or delayed onset of, typhoid disease. These findings are likely to play an important role in improving pediatric vaccination strategies against S. Typhi and other enteric pathogens.

Varying Effect of a Randomized Toddler Home Safety Promotion Intervention Trial by Initial Home Safety Problems.

OBJECTIVES: Toddlers are vulnerable to unintentional injuries. A safety intervention targeting low-income families of toddlers, was effective at improving home safety. The current study examined whether the effect varies by initial home safety problems. METHODS: 277 mother-toddler dyads recruited in the Mid-Atlantic region of the United States during 2007-2010 were randomized into safety promotion (n = 91) or attention-control groups (n = 186). Observers rated participants' homes with a 9-item safety problem checklist at baseline, and at 6- and 12-months follow-up. Initial home safety problems were categorized as multiple (≥ 4 problems) and none/few (< 4). Linear mixed models assessed the moderating effect with a three-way interaction (time, intervention, and initial safety problems). RESULTS: At 12 months, the intervention effect was stronger among families with multiple initial problems than no/few initial problems, with a reduction of 1.55 more problems among the families with multiple problems, compared to the families with no/few problems (b = - 1.55, SE = 0.62, p = 0.013). CONCLUSIONS: Interventions targeting families with multiple safety problems may be more effective than universal programming.

Patient-Reported Outcomes Following Total Hip Arthroplasty: A Multicenter Comparison Based on Surgical Approaches.

BACKGROUND: Comparisons of patient-reported outcomes (PROs) based on surgical approach for total hip arthroplasty (THA) in the United States are limited to series from single surgeons or institutions. Using prospective data from a large, multicenter study, we compare preoperative to postoperative changes in PROs between posterior, transgluteal, and anterior surgical approaches to THA. METHODS: Patient-reported function, global health, and pain were systematically collected preoperatively and at 1, 3, and 6 months postoperatively from patients undergoing primary THA at 26 sites participating in the Comparative Effectiveness of Pulmonary Embolism Prevention After Hip and Knee Replacement (ClinicalTrials.gov: NCT02810704). Outcomes consisted of the brief Hip disability and Osteoarthritis Outcome Score, the Patient-Reported Outcomes Measurement Information System Physical Health score, and the Numeric Pain Rating Scale. Operative approaches were grouped by surgical plane relative to the abductor musculature as being either anterior, transgluteal, or posterior. RESULTS: Between 12/12/2016 and 08/31/2019, outcomes from 3018 eligible participants were examined. At 1 month, the transgluteal cohort had a 2.2-point lower improvement in Hip disability and Osteoarthritis Outcomes Score (95% confidence interval, 0.40-4.06; P = .017) and a 1.3-point lower improvement in Patient-Reported Outcomes Measurement Information System Physical Health score (95% confidence interval, 0.48-2.04; P = .002) compared to posterior approaches. There was no significant difference in improvement between anterior and posterior approaches. At 3 and 6 months, no clinically significant differences in PRO improvement were observed between groups. CONCLUSION: PROs 6 months following THA dramatically improved regardless of the plane of surgical approach, suggesting that choice of surgical approach can be left to the discretion of surgeons and patients without fear of differential early outcomes.

The Effects of Bundled Payment Programs for Hip and Knee Arthroplasty on Patient-Reported Outcomes.

BACKGROUND: Patient-reported outcomes are essential to demonstrate the value of hip and knee arthroplasty, a common target for payment reforms. We compare patient-reported global and condition-specific outcomes after hip and knee arthroplasty based on hospital participation in Medicare's bundled payment programs. METHODS: We performed a prospective observational study using the Comparative Effectiveness of Pulmonary Embolism Prevention after Hip and Knee Replacement trial. Differences in patient-reported outcomes through 6 months were compared between bundle and nonbundle hospitals using mixed-effects regression, controlling for baseline patient characteristics. Outcomes were the brief Knee Injury and Osteoarthritis Outcomes Score or the brief Hip Disability and Osteoarthritis Outcomes Score, the Patient-Reported Outcomes Measurement Information System Physical Health Score, and the Numeric Pain Rating Scale, measures of joint function, overall health, and pain, respectively. RESULTS: Relative to nonbundled hospitals, arthroplasty patients at bundled hospitals had slightly lower improvement in Knee Injury and Osteoarthritis Outcomes Score (-1.8 point relative difference at 6 months; 95% confidence interval -3.2 to -0.4; P = .011) and Hip Disability and Osteoarthritis Outcomes Score (-2.3 point relative difference at 6 months; 95% confidence interval -4.0 to -0.5; P = .010). However, these effects were small, and the proportions of patients who achieved a minimum clinically important difference were similar. Preoperative to postoperative change in the Patient-Reported Outcomes Measurement Information System Physical Health Score and Numeric Pain Rating Scale demonstrated a similar pattern of slightly worse outcomes at bundled hospitals with similar rates of achieving a minimum clinically important difference. CONCLUSIONS: Patients receiving care at hospitals participating in Medicare's bundled payment programs do not have meaningfully worse improvements in patient-reported measures of function, health, or pain after hip or knee arthroplasty.